Thursday 16 December 2010

T 1728/07 – On Chemical Nonsense


This decision contains an interesting discussion of whether a correction of chemical formulae in the claims led to an inadmissible extension.

Claim 1 of the sole request before the Board was very similar to claim 5 of the patent as granted:

1. A process for producing florfenicol ([R-(R*, S*)]-2,2,-dichloro-N-[1-(fluoromethyl)-2-hydroxy-2-[4-ethylsulfonyl) phenyl]ethyl]acetamide), which comprises: (a) preparing a compound of formula (I):


wherein R is CH3S02; and R” is aryl, halo aryl, benzyl, substituted benzyl, C1 to C6 alkyl, C3 to C7 cycloalkyl, and haloalkyl, and the configuration of the oxazoline ring is 4R trans by contacting a compound of formula II:


wherein R is as described above, and R’ is H, C1 to C6 alkyl, C3 to C7 cycloalkyl, benzyl, substituted benzyl, or aryl;
with a reducing agent in a protic solvent, in a suitable reaction vessel, to obtain a compound of formula III:


wherein R is as described above,
(b) then in the same reaction vessel reacting said compound of formula III, with a compound of the formula IV:

R" - C ≡ N   (IV)

to obtain a compound of the formula I, and
(c) converting said compound of formula (1) to florfenicol.

Here is what the Board had to say on the alleged inadmissible extension:

[2.1.1] The sole objection raised under A 100(c) concerned the question of whether or not the amendments of the structural formulae representing oxazoline derivatives, found to be allowable under R 88 EPC 1973 (now R 139 EPC 2000) during examination proceedings, introduced subject-matter extending beyond the content of the application as filed. Since these formulae are still present in the main request […], it must be decided whether these amendments represent corrections of an obvious error within the meaning of R 139.

[2.1.2] Throughout the patent application as originally filed, the compounds of formula (I) are depicted as bearing an amino substituent at position 4 of the oxazoline ring, as illustrated by the following formula appearing in claim 1 as originally filed […]:


In the corresponding formulae disclosed in the main request, and in the specification of patent in suit, the amino substituent at position 4 of the oxazoline ring (H2N-) has been replaced by hydrogen (H-).


According to R 139, second sentence,
“the correction must be obvious in the sense that it is immediately evident that nothing else would have been intended than what is offered as the correction”.
This means that it must be immediately apparent to the skilled person that (i) an error had occurred and (ii) how it should be corrected.

[2.1.3] Concerning requirement (i), it is noted that the application as originally filed discloses the oxazoline compounds of formula (I) as being obtained by reaction of an aminodiol of formula (III) with a nitrile of formula (IV) […]. In examples 1 and 2, the aminodiol sulfone, referred to as ADS […], is reacted with benzonitrile and dichloroacetonitrile, respectively.

Mapping atoms from the starting material to product, the skilled person would immediately recognise that there was an inconsistency in the substitution pattern of the carbon atom bearing an amino substituent in formula (III) and the corresponding carbon atom in formula (I), that is, between the H2N┼H fragment in the former and the H2N┼N fragment in the latter.

Furthermore, in the application as originally filed, it is stated that “the present invention relates to intermediates to florfenicol” […], which is a known compound having the following structure (reproduced from document D2):


On examining the structure of florfenicol (see 2’-position) and comparing it to that of formula (III), the skilled person would have immediately recognised that the H2N┼H fragment was intended to be conserved in the desired end product, and would therefore have identified the H2N┼N fragment in formula (I) as being erroneous.

This would have further been confirmed by the fact that the configuration at the oxazoline ring is specified to be “4R trans” in the application as originally filed […]. The term “trans” in this context can only be intended to denote the relative arrangement on opposite sides of the ring of a substituent at position 4 and a substituent at position 5. The skilled person would therefore note a further contradiction, since the designation “trans” does not make any chemical sense for the structure depicted for formula (I) as originally filed, owing to the presence of two substituents at position 4.

The [opponent’s] argument that it could not be excluded that formula (I) as originally filed was in fact the intended structure owing to the use of the terms “analogs” and “comprising” is not convincing: There is no mention whatsoever in the originally filed application of the presence of an oxidising agent or of the possibility of an additional oxidising step. It is noted that the error in the oxazoline formula is also present in the examples, where an oxidising agent is certainly not present. Moreover, the wording used in claim 1, step (b), namely, “reacting a compound of formula III, with a compound of the formula IV ... to obtain a compound of the formula I” (emphasis added) makes it clear that the compound of formula (I) is the direct product of the reaction between the compounds of formulae (III) and (IV) […].

The skilled person would therefore recognise that an oxidation of the carbon atom at position 4 of the oxazoline ring was not intended and disregard this as being a chemical nonsense, particularly in view of the stated aim of providing “an efficient and economical process for preparing florfenicol” […]. As explained above, an oxazoline intermediate containing an H2N┼N fragment would not be suited to this aim.

Therefore, the board concludes that the skilled person would have no doubt that an error had occurred in the structure depicted for formula (I) as originally filed (cf. requirement (i)).

[2.1.4] With respect to requirement (ii), it must be decided whether the corrected feature is directly and unambiguously derivable from the content of the application as originally filed taken as a whole.

The application as originally filed contains the following cross-reference to document D9 […]:
“The intermediates described in the present specification can be used to prepare florfenicol as can be seen, for example, in U.S. Pat. No. 4,876,352, which is hereby incorporated by reference”.
The only intermediates disclosed in document D9 that match those disclosed in the present application as originally filed are the oxazolines of formula (II) […]. Specific embodiments thereof are disclosed in document D9 […], and as starting materials in the examples, for example, in examples 7 and 8 for the synthesis of florfenicol. In all these intermediates, the oxazoline ring bears a hydrogen atom and not an amino substituent at the position 4. Based on this information, the person skilled in the art would have no doubt that the H2N- substituent present in the pictorial representations of formula (I) was a misprint that should be replaced by H-, thus removing all the contradictions outlined above.

The [opponent’s] argument that the skilled person would not know how to correct the error once detected, is not considered to be convincing. It is true that the formation of a second regioisomer is possible in the reaction of an aminodiol of formula (IV) with a nitrile of formula (III) (cf. e.g. document D2, page 5292, scheme, compounds 6 and 8:


document D8, column 1, lines 25 to 30:


and document D21, formula (I):


However, it is evident from the cross-reference to document D9 that this is not the intended product, since said second regioisomer is not disclose therein. Moreover, the skilled person would a priori not consider the structure of the second regioisomer as a possible correction since it is structurally remote from the erroneous structure and does not include a stereocentre at position 4 of the oxazoline ring; the required “4R trans” configuration is therefore not possible for this structure.

Thus, the second requirement for allowing a correction in the sense of R 139 is also fulfilled in the present case.

[2.1.5] Accordingly, the amendment to formula (I) is allowable under R 139 and does not introduce subject-matter that extends beyond the content of the application as originally filed. The ground for opposition according to A 100(c) does not therefore prejudice the maintenance of the patent on the basis of the main request.

[2.2] The [opponent] did not raise any further objections under A 123(2) and A 123(3) resulting from the amendments made to the main request […], and the board sees no reason to differ. The amended set of claims of the main request is therefore also considered to meet the requirements of A 123(2) and A 123(3).

Personally, I find the Board quite generous, and I am somewhat intrigued by its extended use of the cross-referenced document; did not T 200/89 state that the proposed correction must be obvious to such a skilled reader on reading the patent text in its entirety but in isolation, and without reference to any other documents (such as the file history)” ? Documents incorporated by reference might be an exception though. Having said that, I have to admit that I am not much of a chemist and, therefore, I shall leave the debate to those skilled in this art.

Should you wish to download the whole decision, just click here.

To have a look at the file wrapper, click here.

5 comments:

pat-agoni-a said...

It has been said, that corrections under this rule are in fact superfluous, since either
a) they are immediately obvious and therefore there is no real need to correct them or
b) not allowable.

Kimiko Loko said...

I agree wuth pat-agoni-a. I allways say that "The only errors which can be corrected are those which or not needed to be corrected"

Myshkin said...

I do not agree if the error is in the claims, in which case Art. 84 will usually make the correction mandatory.

In addition, it is hard to defend why obvious errors in the description or drawings, when spotted, should not be corrected. I agree that Art. 83 will usually not require correction of an error, and relying on the support-requirement of Art. 84 might be too far fetched, but there is simply no good reason for not correcting evident mistakes that might make the patent less accessible to the public.

pat-agoni-a said...

I don´t agree that A. 84 makes the correction of an obvious error in the claims mandatory.

It the error and its correction are obvious there can be no lack of clarity or lack of support by that fact.

However, I agree that it looks nicer, but that is a different category than necessity.

Myshkin said...

Clarity is more than "we know what you wanted to say".

If the correction of an obvious error is partly based on the description, there cannot be real doubt that such a correction is necessary for compliance with Art. 84, since the claims should be clear from their wording alone. The same holds if the fact that there is an error in a claim is only evident in the light of the description.

Other clear examples (at least in my view) are the correction of incorrect claim dependencies (not always but sometimes possible under R. 139), and the correction of drafting mistakes such as "a method according to claim 1 ..." where claim 1 is an apparatus and the claim clearly should have read "an apparatus according to claim 1 ...".

I could come up with many more specific examples, but in my view it is a general rule that a claim whose wording contains a clear mistake is unclear in the sense of Art. 84.